We have identified in human brain a peanut agglutinin binding polypeptide with approximate mw of 105,000 (gp105). It is in white matter, but not in gray matter and it is present in isolated myelin. We have isolated gp105 and done some biochemical characterization on it. Approximately 20 dk of the apparent mw of gp105 is contributed by an N-linked glycan of the high mannose variety and 10 kd by an N-linked glycan of the complex variety. Gp105 also contains some O-linked carbohydrate. Gp105 is linked to membranes through a phosphotidylinositol intermediate. We have raised polyclonal antibodies specific for gp105 and immunohistochemica/staining of adult human tissue using affinity purified antibodies indicates that it is confined to CNS myelin. We have also been able to demonstrate gp105 in isolated ovine oligodendrocytes. Gp105 contains the HNK-1 epitope which is common to many abhesion molecules in the nervous system. In this grant application we propose to study further the structure of gp105, try to determine its function and examine gp105 in the context of the pathogenesis of multiple sclerosis. To accomplish this we propose to do the following: 1) to raise more ployclonal and monoclonal antibodies against gp105, 2) to study immunohistochemical and immunochemical distribution of gp105 in normal and M.S. brains, and in neural cells in tissue culture, 3) to measure the level of gp105 in CSF from M.S. patients and controls, 4) to determine whether gp105 influences adhesion between cells, 5) to determine whether M.S. patients have in their serum of CSF antibodies against gp105 and 6) to clone and sequence cDNA for gp105 in order to be able to deduce its primary structure. We believe that studies of gp105 may provide us with important information on the biology of oligodendrocytes and even on the pathogenesis of M.S.